corrected qt interval effects of trastuzumab emtansine (t-dm1) in patients with human epidermal growth factor receptor 2 (her2)-positive locally advanced or metastatic breast cancer and the safety and tolerability of combined t-dm1 and pertuzumab in patients with early disease progression

Conditions: Metastatic Breast Cancer

Summary: this is a multicenter, open-label, single-arm phase ii study designed to evaluate the effect of t-dm1 on the duration of corrected qt (qtc) interval in patients with her2-positive locally advanced or metastatic breast cancer and to make preliminary assessments regarding the safety, tolerability, and efficacy of combined t-dm1 and pertuzumab in patients with early disease progression. the qt interval is a measure of time between the start of the q wave and the end of the t wave in the heart's electrical cycle. the qtcf interval is the qt interval as calculated using fridericia's correction; the qtcb interval is the qt interval as calculated using bazett's correction.


Eligibility criteria:
inclusion criteria: * histologically documented, locally advanced, or metastatic breast cancer; measurable and/or non-measureable but evaluable disease is permitted * her2-positive disease * history of prior trastuzumab therapy * life expectancy ≥ 90 days as assessed by the investigator * negative urine pregnancy test ≤ 72 hours prior to cycle 1 day 1 for all women of childbearing potential * for patients of childbearing potential, agreement to use one highly effective form of contraception or two effective forms of contraception for the duration of the study treatment(s) and for 4 months after the last dose of t-dm1 or 6 months after the last dose of pertuzumab, if applicable exclusion criteria: * any chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or biologic therapy for the treatment of breast cancer within 2 weeks of the first study treatment * prior t-dm1 or pertuzumab therapy * history of intolerance (such as grade 3-4 infusion reaction) and/or adverse events related to trastuzumab * grade ≥ 2 (based on national cancer institute common terminology criteria for adverse events \[nci ctcae\] v3) peripheral neuropathy at the time of or within 3 weeks prior to the first study treatment * brain metastases that are untreated or progressive or have required any type of therapy, including radiation, surgery, and/or steroids, to control symptoms from brain metastases within 60 days prior to the first study treatment * history of cardiac disease, unstable angina, symptomatic congestive heart failure (chf) (class ≥ ii per the new york heart associate \[nyha\] guidelines), myocardial infarction, or ventricular arrhythmia ≤ 6 months prior to cycle 1, day 1 * implantable pacemaker or automatic implantable cardioverter defibrillator * congenital long qt syndrome or family history of long qt syndrome * current uncontrolled hypertension * current treatment with medications that alter cardiac conduction (e.g., digitalis, beta-blockers, or calcium channel blockers) or medications that are generally accepted to have a risk of causing torsades de pointes (tdp) * current known active infection with human immunodeficiency virus (hiv), hepatitis b virus, or hepatitis c virus * major surgical procedure or significant traumatic injury within 28 days prior to first study treatment, or anticipation of the need for major surgery during the course of study treatment

Keywords: mbc tdm1 armed herceptin herceptin trastuzumab emtansine